As a faculty member in the Department of Anesthesiology at the University of Florida, I have previous experience as a principal investigator for industry-funded clinical trials, but no formal training in research design and data analysis. The primary intent of this K01 proposal is to enter a three-year career development program that will allow me to redirect my research efforts towards evaluating the influence of anesthesia and surgery on cognitive aging. During the first year of the proposal, I will complete a Master's Degree in Medical Science in Clinical Investigation with electives in cognitive aging and the neurosciences. The final two years of the career development award will be devoted to intensive training in neurocognitive testing and clinical research. The proposed research plan is designed to characterize the incidence, risk factors, and neurpsychological profile of postoperative cognitive dysfunction (POCD). Our preliminary data indicate that POCD is common in elderly patients undergoing orthopedic joint replacement surgery. During the early stages of the training program, I will work with my mentors to design a prospective study to determine if intraoperative embolic events during total knee arthroplasty (TKA) correlate with the occurrence of POCD. We will also determine if changes in medullary instrumentation techniques influence the incidence of embolic events and postoperative cognitive outcome. This study will use magnetic resonance imaging (MRI), transesophageal echocardiography, and transcranial doppler monitoring to identify the mechanisms and sites of cerebral injury during TKA. At the completion of my career development training, I will be uniquely trained in three major approaches to the investigation of cognitive changes in older adults: clinical assessment, neuroscience and neuroimaging, and psychometric/neuropsychological approaches to the assessment of everyday cognitive functioning. I plan to use this expertise to become the director of a Division of Clinical Research. This research division will participate in multidisciplinary research investigating aging issues in the perioperative period. Initial research will evaluate the etiology of POCD and interventions to decrease or prevent this complication. Given the breadth of my proposed training program, I will be able to interact with and serve as a mentor for anesthesiologists and also the broader corpus of scientists, both clinical and basic, interested in aging and neuroscience.